The purpose of this program is to bring together several independent investigators so that they can take advantage of an unusual opportunity both to advance the basic information we have about the biology of connective tissues and to explore the possible implications that this information may have for our understanding of diseases which affect these tissues. A major part of the work on diseases will focus on the relatively well-defined genetic diseases osteogenesis imperfecta and Ehlers-Danlos syndrome. These diseases will be studied both because of their own intrinsic importance and because of the implications that several recent discoveries about these diseases have for more common conditions such as osteoporosis, osteoarthritis, diabetes and related disorders. The research will include collaborative studies in the following specific areas: Studies on the enzyme which cleaves the N-terminal propeptide in the conversion of procollagen to collagen (CO1); studies on the enzyme which cleaves the C-terminal propeptide in the conversion of procollagen to collagen (CO2); formation of collagen fibers in vitro by the enzymatic cleavage of procollagen (CO3); structure and function of altered procollagens synthesized by fibroblasts from patients with osteogenesis imperfecta and related disorders (CO5).